Globe and Mail

Second Opinion
Be skeptical about the Herceptin hype
By ANDRE PICARD

Thursday, August 4, 2005 Page A15

The breast cancer drug trastuzumab (better known by its brand name
Herceptin) has had more than its share of good press. It has been described
as "the biggest cancer breakthrough in a decade," "a life-saving drug" and
the "next best thing to a cure."

The laudatory words from some oncologists and patient advocates, along with
extensive media coverage, have placed enormous pressure on public health
plans to fund the treatment. Much of the debate has focused on the price
Genentech Inc. is asking for Herceptin -- between $35,000 and $45,000,
depending on the patient's weight.

Providing Herceptin to a select group of breast cancer patients would
effectively double the cost of treatment and add $150-million a year to the
health-care tab.

But that's a small price to pay for a miracle, right?

 Let's leave the discussion of pricing for another day and focus instead on
the other numbers, the ones that tell us just how effective Herceptin can
be in ridding women of breast cancer. (Before going any further, let's
remember that Herceptin is designed only for breast cancer sufferers who
produce too much HER-2 protein -- about one in four cases.)

The most eye-popping claim is that, for this select group, the drug cuts
the risk of recurrence by half. In clinical trials, women who took
Herceptin along with a standard chemotherapy drug saw their risk of
recurrence fall 52 per cent, compared to women who received chemo alone.
That is an impressive relative risk reduction.

But what matters in the real world is absolute (not relative) risk
reduction. Practically speaking, 15 per cent of women taking Herceptin and
chemo had a recurrence of breast cancer within four years of diagnosis,
compared to 33 per cent of women who took chemo alone. That is an absolute
risk reduction of 18 per cent.

Nobody wants a recurrence, but what matters ultimately is survival.
Herceptin, according to the studies, cut the death rate by one-third. That
sounds impressive, but relative risk reductions always do. In reality, the
difference in the death rate between the Herceptin and non-Herceptin groups
was 2 per cent after three years, and 4 per cent after four years.

Based on those numbers, can we honestly say that Herceptin is an essential
lifesaving drug?

Like every drug, Herceptin has side effects. In the clinical trials, the
rate of heart failure was 3 per cent higher among women receiving
Herceptin. Is trading breast cancer for heart failure the next best thing
to a cure?

When it comes to drugs, miracles are often short-lived. Tamoxifen was once
the next best thing to a cure for postmenopausal women with breast cancer.
Despite early promise, follow-up studies showed that after five years of
use, the drug actually increased the risk of recurrence, along with
increasing the risk of endometrial cancer.

Then along came letrozole (a drug taken after five years of tamoxifen),
which in studies also cut the risk of recurrence by half. The jury is still
out on whether the medication will increase the risk of cardiovascular
disease.

But at least physicians and women prescribed the earlier drugs have access
to the full data. The most troubling aspect of the Herceptin story is how
little evidence of its effectiveness has been published in peer-reviewed
medical journals.

Clinical trials testing Herceptin for treatment of early-stage breast
cancer were cut short in April after an interim analysis showed "better
than expected" results. Halting research early is controversial at the best
of times. When it has been done in the past -- most famously in the study
declaring hormone replacement therapy to increase the risk of breast
cancer, heart attacks and stroke -- the data were published immediately.

The Herceptin data have been presented selectively at scientific
conferences, in press releases and news reports. That's bad science. It's
also pretty flimsy evidence on which to make declarations of miracles, and
on which to base tens of millions of dollars in spending.

Women are being advised to take this treatment, and provincial health plans
forced to make decisions on funding, based on inadequate data.

Perhaps it's not fair to single out Herceptin. Every pharma company dreams
of this kind of buzz for its drug. But it is, in the words of Herceptin's
promoters themselves, the dawning of a new era where we will target disease
at its genetic roots, with costly new drugs.

This requires a new era of rigorous, dispassionate analysis that provides
health professionals and patients with timely data on effectiveness and
cost-effectiveness of all drugs.

Herceptin has not met this test.

In the months and years to come, there will be many vaunted pharmaceutical
miracles, many next-best-things-to-a-cure. They must be kept in
perspective. We cannot, in our desperate desire for good news, suspend our
critical faculties.

When it comes to Herceptin, some healthy skepticism is, well, quite
healthy.

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